Colorectal cancer (CRC) remains the second leading cause of cancer of deaths underscoring the need for more effective preventive strategies. Indeed, while colonoscopy is effective in reducing CRC, it suffers from up to 30% polyp miss rate even among expert endoscopists and marginal ability to determine frequency of colonoscopy. Thus, technological advances are necessary to allow more effective implementation of colonoscopy into primary population screening. Our multidisciplinary CRC prevention group has been interested in bridging biomedical optics to clinical medicine. With the aid of an R21 grant from the NCI, we have recently developed polarization-gated visible light spectroscopy for accurate quantitation of microvascular blood content. Using this approach we have recently published our novel observation that early increase in blood supply (EIBS) in the colonic microcirculation occurs early during neoplastic transformation and precedes formation of adenomas, aberrant crypt foci and other currently known markers of CRC. We envision that, in the long-term, concomitantly measuring EIBS could guide colonoscopy by allowing a colonoscopist to identify colonic segments that require more intensive scrutiny and, since in humans EIBS is expected to precede tumorigenesis by at least a decade, also enable accurate determination of optimal colonoscopic frequency. In order for EIBS assessment to achieve clinical fruition it is critical to demonstrate the ability of this approach to predict concurrent and future neoplastic lesions. We plan to assess this using serial measurement of EIBS in the azoxymethane-treated rat model. We will use the carcinogen treatment regimen that repeatedly induces adenomas or carcinomas in ~50% of animals. To enable EIBS measurements in vivo, we will develop a rat colonoscope-compatible fiber-optic polarization- gated spectroscopy probe. We will perform rat colonoscopies and measure EIBS at various premalignant and malignant time-points in order to formulate and then prospectively validate prediction rules for future adenomas based on microvascular blood content. Thus, this project will allow development of a technique that will validate EIBS for CRC detection/screening paving the way for future clinical trials.